In Chinese traditional medicine, Zedoariae Rhizoma (the rhizome of Curcuma zedoaria), Saussureae Radix (the roots of Saussurea lappa), Nupharis Rhizoma (the rhizome of Nuphar pumilum), and Rhei Rhizoma (the rhizome of Rheum undulatum) has been prescribed for the treatment of "Oketsu" syndrome caused by blood stagnation and inflammation. Inducible NO synthase (iNOS) is involved in pathological processes mediated with overproduction of NO and is expressed in response to pro-inflammatory agents such as interleukin-1β, tumor necrosis factor-α and lipopolysaccharide (LPS) in various cell types including macrophages. Inhibition of iNOS enzyme activity or its induction may have therapeutic effects in various types of inflammation. In the course of our studies on bioactive principles from Chinese herbal medicines, we have found that sesquiterpenes (furanodinene, costunolide, dehydrocostus lactone, santamarine, saussureamines A and B) from Zedoariae Rhizoma and Saussureae Radix, dimeric sesquiterpene thioalkaloids (6-hydroxythiobinupharidine, 6,6'-dihydroxythiobinupharidine, 6-hydroxythio-nuphlutine B) from Nupharis Rhizoma, and stilbenes (rhapontigenin, piceatannol, resveratrol) from Rhei Rhizoma showed NO production inhibitory activity in LPS-activated macrophages. And some structural requirements for the activity was elucidated. Several sesquiterpenes (curcumenone, furanodiene, germacrone, etc.) from Zedoariae Rhizoma and the stilbenes and stilbene glycosides (rhaponticin, piceatannol 3'-O-β-D-glucopyranoside, etc.) from Rhei Rhizoma showed hepato-protective activity in D-galactosamine/LPS-induced liver injury in mice. Many sesquiterpenes from Zedoariae Rhizoma and Saussureae Radix showed vasorelaxant activity in vitro. These results may be related to the treatment effects of those Chinese herbal medicines for "Oketsu" syndrome.
